Introduction: A New Era in Diabetes Care – The Rise of Once-Weekly Insulin Therapy
For decades, people living with diabetes have had to rely on daily insulin injections to manage their blood glucose levels — a routine that often comes with physical, emotional, and practical challenges. But the landscape of diabetes care is rapidly evolving. A revolutionary approach is making headlines: once-weekly insulin therapy.
With novel agents like insulin icodec (from Novo Nordisk) and efsitora alfa (from Eli Lilly), researchers are exploring insulin analogs that can deliver steady glucose control with just a single injection per week. This innovation offers hope for improved adherence, reduced injection burden, and potentially better long-term outcomes.
Let’s explore what weekly insulin therapy really is, how it works, and whether it’s the game changer we’ve been waiting for in diabetes management.
What is once-weekly insulin therapy?
Once-weekly insulin therapy involves using ultra-long-acting insulin analogs that maintain stable blood glucose control for an entire week after a single subcutaneous injection. Unlike traditional basal insulins (like glargine or detemir) that require daily administration, these new insulins release slowly and predictably over seven days.
What are the leading weekly insulin candidates?
Two major weekly insulin analogs are currently leading the development race:
- Insulin Icodec (Novo Nordisk)
- A modified insulin molecule with strong albumin binding and reduced clearance.
- Designed to mimic the effects of daily basal insulin in just one injection per week.
- Advanced to Phase 3 trials (ONWARDS program).
- Efsitora Alfa (LY3209590 by Eli Lilly)
- A once-weekly basal insulin Fc fusion protein.
- Engineered for prolonged action and consistent glucose-lowering effect.
- Has shown promising Phase 2 results in type 2 diabetes patients.
How do once-weekly insulins work?
These analogs have structural modifications (e.g., strong binding to albumin or fusion with IgG Fc fragments) that slow down absorption and degradation. This allows the insulin to:
- Remain in circulation longer.
- Provide consistent basal insulin coverage.
What are the potential benefits of weekly insulin therapy?
Fewer injections – just 1 vs 7 per week.
Improved adherence – better for forgetful or needle-averse patients.
Better quality of life – reduced burden of daily injections.
Comparable or even superior glycemic control – studies show similar HbA1c reduction to daily basal insulins.
Lower risk of hypoglycemia (in some studies) – especially nocturnal episodes
Are there any challenges or risks?
Yes, some considerations include:
- Titration difficulty – Weekly dose adjustments are slower to take effect.
- Missed dose impact – Missing a weekly dose could have more serious consequences.
- Hypoglycemia risk – Although some trials show reduced hypoglycemia, others highlight risk if overdosed.
- Cost and availability – As with all innovations, pricing and insurance coverage may be a barrier.
How do Icodec and Efsitora compare in trials so far?
| Feature | Insulin Icodec | Efsitora Alfa |
|---|---|---|
| Developer | Novo Nordisk | Eli Lilly |
| Dosing Frequency | Once weekly | Once weekly |
| Mechanism | Albumin-binding modified insulin | Fc-fusion protein |
| HbA1c Reduction | Comparable or slightly superior to daily insulin | Comparable to daily insulin |
| Hypoglycemia Rates | Non-inferior, sometimes better | Low risk in early-phase trials |
| Trial Stage | Phase 3 (ONWARDS 1–6) | Phase 2 completed |
Are weekly insulins approved yet?
As of mid-2025, insulin icodec is nearing regulatory approval, with Phase 3 trials completed and data under review. Efsitora is slightly behind in development, pending Phase 3 trial initiation. Approval in some countries may begin within the next 12–18 months, starting with type 2 diabetes.
Who are ideal candidates for weekly insulin?
- Adults with type 2 diabetes needing basal insulin.
- Patients struggling with daily injections or adherence.
- Individuals with cognitive or physical limitations.
- Busy individuals with inconsistent daily schedules.
For now, most trials have excluded type 1 diabetes, pregnant women, and those with unstable insulin needs.
Could weekly insulin replace all daily insulins?
Not yet. Weekly insulin is currently designed to replace basal insulin only — that is, background insulin needs. It is not a substitute for bolus (mealtime) insulin in type 1 diabetes or advanced type 2 cases. However, it’s a significant step forward.
Will this change the future of diabetes management?
Quite possibly. Weekly basal insulin could revolutionize how we initiate and maintain insulin therapy. If long-term studies confirm efficacy, safety, and patient preference, this could dramatically improve outcomes, especially in populations with poor adherence to daily regimens.
Can once-weekly insulin be used for Type 1 diabetes?
Currently, no. Trials for insulin icodec and efsitora have excluded type 1 diabetes patients due to the higher variability in insulin needs and requirement for mealtime (bolus) insulin.
- Some exploratory research may be done in future.
- As of now, it’s only under development for type 2 diabetes.
What are the current trials for Icodec and Efsitora?
Insulin Icodec (Novo Nordisk)
- ONWARDS Clinical Trial Program (6 major Phase 3 trials):
- ONWARDS 1–6 covered insulin-naive patients, switchers from daily insulin, older adults, etc.
- All showed non-inferior or slightly better HbA1c reduction, good tolerability, and patient satisfaction.
- Mild hypoglycemia reported, mostly nocturnal.
🔬 Efsitora Alfa (Eli Lilly)
- Phase 2 trials showed good safety and glucose control.
- Planning for Phase 3 trials is underway.
- Less clinical data available than icodec as of mid-2025.
Which countries have approved insulin icodec?
Approved in Canada (March 2024).
Approved in the EU (April 2024).
Pending approval in the US — under FDA review
Why is FDA approval of icodec delayed?
Hurdles include:
- Long-term safety data — particularly hypoglycemia risk in vulnerable groups.
- Missed dose protocols — FDA wants clarity on how patients should handle skipped or delayed injections.
- Titration complexity — weekly dosing requires different initiation and adjustment strategies.
What will be the cost of weekly insulin?
Exact cost not announced, but expectations are:
- Higher than daily basal insulin, at least initially.
- May be cost-effective long-term due to better adherence and fewer complications.
- Insurance and government subsidies will vary by country.
When will once-weekly insulin be available in Pakistan?
No official launch date yet.
After US or EU FDA approval, rollout in Pakistan could occur within 1–2 years, depending on:
- DRAP approval (Pakistan Drug Regulatory Authority)
- Import strategy by Novo Nordisk or Lilly Pakistan
- Cost-effectiveness assessments
Can once-weekly insulin be combined with GLP-1 drugs (e.g., Semaglutide)?
Yes — and it’s a promising combination.
- Basal insulin + GLP-1 receptor agonist is already a validated therapy.
- Weekly insulin and weekly GLP-1 (like Ozempic) could improve both glycemic control and weight management with minimal injections.
- Trials may soon explore this combo.
How is the dose of weekly insulin calculated?
Conversion formulas are used when switching from daily basal insulin (e.g., glargine).
- Example: Daily dose × 7 = weekly dose, then adjusted for bioavailability.
Titration usually happens every 1–2 weeks, not daily.
Initiation protocols differ for insulin-naïve vs insulin-experienced patients.
What is the risk of hypoglycemia with weekly insulin?
Trials (like ONWARDS) report low to moderate rates, especially during titration or missed meals.
Risk is comparable or lower than daily basal insulin in most cases.
Night-time hypoglycemia was slightly more frequent but manageable.
What about safety of weekly insulin in patients with kidney (renal) impairment?
Weekly insulins are being evaluated in moderate to severe renal impairment.
No major red flags so far with icodec.
Dose adjustment may be needed, and patients should be monitored closely, especially in advanced CKD stages.
How is once-weekly insulin a game changer?
Improves adherence – One weekly dose is easier for forgetful or busy patients.
Reduces injection burden – Just 52 injections per year vs 365.
Better quality of life – For working adults, elderly, needle-phobic, or rural patients.
Potentially lowers healthcare costs – Fewer complications from missed doses.
Enables simplified regimens – Especially in combination with weekly GLP-1s or oral agents.
Could transform insulin uptake in low-resource or high-resistance populations, like South Asia.
Conclusion
Weekly insulin isn’t just a pharmacological innovation — it’s a paradigm shift. With strong clinical trial results and global anticipation, insulin icodec and efsitora could rewrite the future of type 2 diabetes care. While challenges like cost, titration, and regulatory hurdles remain, the benefits for patient adherence and healthcare systems are hard to ignore.
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